Quantum optimization of maximum independent set using Rydberg atom arrays.

Realizing quantum speedup for practically relevant, computationally hard problems is a central challenge in quantum information science. Using Rydberg atom arrays with up to 289 qubits in two spatial dimensions, we experimentally investigate quantum algorithms for solving the maximum independent set problem. We use a hardware-efficient encoding associated with Rydberg blockade, realize closed-loop optimization to test several variational algorithms, and subsequently apply them to systematically explore a class of graphs with programmable connectivity. We find that the problem hardness is controlled by the solution degeneracy and number of local minima, and we experimentally benchmark the quantum algorithm's performance against classical simulated annealing. On the hardest graphs, we observe a superlinear quantum speedup in finding exact solutions in the deep circuit regime and analyze its origins.

Lirentelimab for severe and chronic forms of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

Probing topological spin liquids on a programmable quantum simulator.

Quantum spin liquids, exotic phases of matter with topological order, have been a major focus in physics for the past several decades. Such phases feature long-range quantum entanglement that can potentially be exploited to realize robust quantum computation. We used a 219-atom programmable quantum simulator to probe quantum spin liquid states. In our approach, arrays of atoms were placed on the links of a kagome lattice, and evolution under Rydberg blockade created frustrated quantum states with no local order. The onset of a quantum spin liquid phase of the paradigmatic toric code type was detected by using topological string operators that provide direct signatures of topological order and quantum correlations. Our observations enable the controlled experimental exploration of topological matter and protected quantum information processing.

Controlling quantum many-body dynamics in driven Rydberg atom arrays.

The control of nonequilibrium quantum dynamics in many-body systems is challenging because interactions typically lead to thermalization and a chaotic spreading throughout Hilbert space. We investigate nonequilibrium dynamics after rapid quenches in a many-body system composed of 3 to 200 strongly interacting qubits in one and two spatial dimensions. Using a programmable quantum simulator based on Rydberg atom arrays, we show that coherent revivals associated with so-called quantum many-body scars can be stabilized by periodic driving, which generates a robust subharmonic response akin to discrete time-crystalline order. We map Hilbert space dynamics, geometry dependence, phase diagrams, and system-size dependence of this emergent phenomenon, demonstrating new ways to steer complex dynamics in many-body systems and enabling potential applications in quantum information science.

Historic tobacco legislation in Israel: a moment to celebrate.

BACKGROUND: Israel was once a leader in tobacco control, but fell behind other countries, particularly during the past decade, as smoking rates stagnated. TEXT: Landmark tobacco control legislation, which banned advertising (with the exception of the print press) and limited marketing, was passed in Israel on Dec. 31rst, 2018. The changes occurred following years of attempts which culminated in successful last-minute efforts to promote the legislation just before the early disbanding of the 20th Knesset (Israeli Parliament). Regulations concerning marketing and advertising were substantially strengthened to address all tobacco, nicotine and smoking products. Digital media was included for the first time. Electronic cigarettes, which were previously largely unregulated, now fall under existing tobacco legislation. The changes overcame intense opposition from the tobacco lobby, and occurred despite the fact that the basic elements for prevention policy postulated by the Richmond model were not in place. CONCLUSIONS: This legislation represents an important and long-awaited change in Israeli tobacco control policy. Many deficiencies in existing tobacco control regulation were overcome, and some measures went beyond current international regulations. The cohesive partnership between legislators, public health organizations and professionals, advocacy groups, academia, and leading journalists was critical to this success. The progress was lauded by the World Health Organization with its highest award for tobacco control, which was presented to Smoke Free Israel. This case study provides important lessons for up-to-date tobacco control policy, in the age of rapid global changes in the tobacco, vaping and nicotine landscape.

Generation and manipulation of Schrödinger cat states in Rydberg atom arrays.

Quantum entanglement involving coherent superpositions of macroscopically distinct states is among the most striking features of quantum theory, but its realization is challenging because such states are extremely fragile. Using a programmable quantum simulator based on neutral atom arrays with interactions mediated by Rydberg states, we demonstrate the creation of "Schrödinger cat" states of the Greenberger-Horne-Zeilinger (GHZ) type with up to 20 qubits. Our approach is based on engineering the energy spectrum and using optimal control of the many-body system. We further demonstrate entanglement manipulation by using GHZ states to distribute entanglement to distant sites in the array, establishing important ingredients for quantum information processing and quantum metrology.

The Q359K/T360K mutation causes cystic fibrosis in Georgian Jews.

BACKGROUND: The Q359K/T360K mutation, described in Jewish CF patients of Georgian decent, is of questionable clinical significance. METHODS: Clinical records of patients with the Q359K/T360K mutation from three CF centers were studied for phenotypic expression and putative mechanism of dysfunction. Computer models of mutant CFTR were constructed. RESULTS: Nine patients (4 homozygous) of Georgian Jewish origin were included. Age at diagnosis was 9.4 (0.25-38.2) years, median (range). Sweat chloride was 106 ±â€¯13 meq/L, mean ±â€¯SD. Nasal Potential Difference performed in three, was abnormal. All had pulmonary symptoms since early childhood and bronchiectasis. Median FEV1 was 88 (40-121)%. Five had chronic mucoid P. aeruginosa. Homozygous patients were pancreatic insufficient. Enzyme supplementation was initiated at 3.8 (1-14.7) years, median (range). Structural models hint at possible interference of this mutation with transmembrane chloride transport. CONCLUSION: In our cohort, the Q359K/T360K mutation resulted in a severe CF phenotype, although with residual early CFTR function. The CFTR2 database should consider defining this mutation as CF-causing.

Amyloid fibril polymorphism: a challenge for molecular imaging and therapy.

The accumulation of misfolded proteins (MPs), both unique and common, for different diseases is central for many chronic degenerative diseases. In certain patients, MP accumulation is systemic (e.g. TTR amyloid), and in others, this is localized to a specific cell type (e.g. Alzheimer's disease). In neurodegenerative diseases, NDs, it is noticeable that the accumulation of MP progressively spreads throughout the nervous system. Our main hypothesis of this article is that MPs are not only markers but also active carriers of pathogenicity. Here, we discuss studies from comprehensive molecular approaches aimed at understanding MP conformational variations (polymorphism) and their bearing on spreading of MPs, MP toxicity, as well as MP targeting in imaging and therapy. Neurodegenerative disease (ND) represents a major and growing societal challenge, with millions of people worldwide suffering from Alzheimer's or Parkinson's diseases alone. For all NDs, current treatment is palliative without addressing the primary cause and is not curative. Over recent years, particularly the shape-shifting properties of misfolded proteins and their spreading pathways have been intensively researched. The difficulty in addressing ND has prompted most major pharma companies to severely downsize their nervous system disorder research. Increased academic research is pivotal for filling this void and to translate basic research into tools for medical professionals. Recent discoveries of targeting drug design against MPs and improved model systems to study structure, pathology spreading and toxicity strongly encourage future studies along these lines to provide an opportunity for selective imaging, prognostic diagnosis and therapy.

Body mass index and infectious disease mortality in midlife in a cohort of 2.3 million adolescents.

BACKGROUND: Obesity was linked to altered immunity, but also to favorable outcomes among patients with infectious disease (ID) in some settings. We assessed the association between adolescent body mass index (BMI) and ID mortality. METHODS: BMI of 2 294 139 Israeli adolescents (60% men; age 17.4±0.3 years) was measured between 1967 and 2010. The outcome, obtained by linkage with official national records, was death due to ID as the underlying cause. Multivariable Cox proportional hazards models were applied. RESULTS: During 42 297 007 person-years of follow-up (median 18.4 years), there were 689 deaths from ID (mean age 44.1±10.5 years). Adjusted hazard ratios (HR) were 1.039 (1.011-1.068) and 1.146 (1.099-1.194) among men and women, respectively, per unit increment in BMI (P for sex interaction=4.4 × 10-5). Adjusted hazard ratios among men were 1.2 (1.0-1.5), 1.9 (1.4-2.5) and 2.5 (1.5-4.2) for those with high-normal BMI (22.0-24.9 kg m-2), overweight and obese, respectively, compared with the 18.5⩽BMI<22 kg m-2 reference group, and 1.7 (1.1-2.6), 2.6 (1.6-4.3) and 6.6 (3.3-13.1) among women, respectively. The increased risk among underweight (<18.5 kg m-2) boys was attenuated when the study sample was restricted to those with unimpaired health at baseline. A multivariable spline model indicated a minimum risk for total ID mortality at 20.7 and 18.0 kg m-2 for men and women, respectively, with significantly increased risk seen above adolescent BMI values of 23.6 and 24.0 kg m-2, respectively. The association with BMI was particularly evident for bacterial infections (predominantly sepsis), airways and central nervous system infections (63% of the ID deaths). CONCLUSIONS: Adolescent overweight and obesity were strongly associated with ID mortality, especially of bacterial origin and among women.

Paternal age and risk of testicular germ cell tumors: a cohort study of 1,000,000 men.

Testicular germ cell tumors (TGCT) are the most frequent cancer among young men, with increasing incidence worldwide. Advanced paternal age has been linked to adverse health outcomes in offspring, but reports on the association of paternal age with TGCT are few and inconsistent. We aimed to examine the relationship of paternal age (PAB) at birth with the risk of TGCT and by histologic type: seminoma and non-seminoma. A population-based cohort of 1,056,058 males, examined at ages 16-19 between the years 1980-2011, was linked to the Israel National Cancer Registry to obtain incident TGCT through 2012. We applied multivariable Cox regression. During 16.5 million person-years of follow-up, 1247 incident cases (604 seminomas and 643 non-seminomas) were detected. Increasing PAB was linearly associated with lower risk of TGCT (HRper year  = 0.983, 95% CI: 0.974-0.993, p = 0.001), after adjustment for year of birth, years of education, height, cryptorchidism history and origin, and also with additional adjustment for maternal age at birth (MAB) (HRper year  = 0.980: 0.965-0.995, p = 0.008). The association was stronger for seminoma (HRper year  = 0.968: 0.946-0.989, p = 0.004) and persisted in a subset adjusted for sibship size (HRper year  = 0.950: 0.917-0.983, p = 0.003). In the fully adjusted model, young PAB (15-24 vs. ≥30) was a risk factor for seminoma (HR = 1.41: 1.07-1.85, p = 0.014). In models adjusted for PAB, MAB was not associated with risk of TGCT. In conclusion, our findings suggest that young paternal age is a risk factor of TGCT, especially seminoma. The findings warrant further investigation into the possible impact of young paternal age on their offsprings' testes.

Connecting the Sequence-Space of Bacterial Signaling Proteins to Phenotypes Using Coevolutionary Landscapes.

Two-component signaling (TCS) is the primary means by which bacteria sense and respond to the environment. TCS involves two partner proteins working in tandem, which interact to perform cellular functions whereas limiting interactions with non-partners (i.e., cross-talk). We construct a Potts model for TCS that can quantitatively predict how mutating amino acid identities affect the interaction between TCS partners and non-partners. The parameters of this model are inferred directly from protein sequence data. This approach drastically reduces the computational complexity of exploring the sequence-space of TCS proteins. As a stringent test, we compare its predictions to a recent comprehensive mutational study, which characterized the functionality of 204 mutational variants of the PhoQ kinase in Escherichia coli We find that our best predictions accurately reproduce the amino acid combinations found in experiment, which enable functional signaling with its partner PhoP. These predictions demonstrate the evolutionary pressure to preserve the interaction between TCS partners as well as prevent unwanted cross-talk. Further, we calculate the mutational change in the binding affinity between PhoQ and PhoP, providing an estimate to the amount of destabilization needed to disrupt TCS.

Molecular characterization and antibiotic resistance of group G streptococci in Israel: comparison of invasive, non-invasive and carriage isolates.

Beta-hemolytic group G streptococci (GGS) are increasingly recognized as a source of substantial morbidity, causing mild to severe sporadic infections as well as outbreaks. The purpose of this study was to determine the genetic diversity and antibiotic resistance of GGS in Israel in order to aid in prevention and control. A total of 325 GGS isolates were collected in Israel between 2007 and 2011 from three determined settings: (1) carriage (n = 60), an observational longitudinal carriage study in the IF, (2) non-invasive (n = 166), clinical sporadic and epidemic non-invasive cases in the IDF, and (3) invasive (n = 99) cases of bacteremia collected during this period in Israel from a similar age group, at the national Streptococcal Reference Center. All isolates were characterized genetically and by their antibiotic-resistance profile. emm typing revealed 35 distinct types and subtypes among 228 S. dysgalactiae subsp. equisimilis (SDSE) isolates, with high genetic diversity. An additional 97 GGS were identified as Streptococcus anginosus (SAG). The proportion of SDSE was higher in the invasive (100 %) and non-invasive (63.8 %) isolates compared to the carriage ones (38.3 %). Clindamycin, erythromycin, azithromycin and tetracycline resistance was detected in 6.6 %, 8.6 %, 9.7 % and 37.6 % of isolates, respectively. Overall, the most resistant isolates were in the invasive group and the fewest were in the SAG group. Considerable genetic diversity and common antibiotic resistance were revealed among GGS strains which differed according to the epidemiologic settings. Further clinical, epidemiological and basic research of GGS as a pathogen is warranted.

Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns.

Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS ) and anopenile distance (AGPAP ) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, ß=-0.48; 95% confidence interval, -0.93, -0.02), MEHHP (-0.48; -0.92, -0.05), mono-2-ethyl-5-carboxypentyl (MECPP, -0.51; -1.01, -0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono-2-ethyl-5-hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (ß = -1.73; 95% confidence interval, -3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these associations in humans.

Phthalate exposure and semen quality in fertile US men.

Several experimental and observational studies have demonstrated the antiandrogenicity of several phthalates. However, there is limited evidence of an association between phthalate exposure in adult life and semen quality. The aim of this study was to examine phthalate exposure during adulthood in relation to semen quality in fertile US men. This multi-center cross-sectional study included 420 partners of pregnant women who attended a prenatal clinic in one of five US cities during 1999-2001. Nine phthalate metabolites [mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP)], as well as mono-n-butyl phthalate (MBP) and mono-isobutyl phthalate (MiBP), mono (three carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP)] were measured in urine collected at the same time as the semen sample. We regressed natural log-transformed (ln) sperm concentration, ln(total sperm count), ln(total motile sperm count), percent motile spermatozoa, and percent spermatozoa with normal morphology on each of the nine natural log-transformed metabolite concentrations and on the molar-weighted sum of DEHP metabolites in separate models. We fit unadjusted models and models that adjusted for confounders determined a priori. In unadjusted models, ln(MiBP) was significantly and positively associated with motility and ln(MBzP) significantly negatively associated with ln(total sperm count). In adjusted linear models, urinary metabolite concentrations of DEHP, DBP, DEP, and DOP were not associated with any semen parameter. We found an inverse association between ln(MBzP) concentrations and sperm motility (ß = -1.47, 95% CI: -2.61, -0.33), adjusted for ln(creatinine concentration), geographic location, age, race, smoking status, stress, recent fever, time from sample collection and time to complete analysis. Several sensitivity analyses confirmed the robustness of these associations. This study and the available literature suggest that impacts of adult exposure to phthalates at environmental levels on classical sperm parameters are likely to be small.

Smoking initiation among Israeli adolescents: a 24-year time-to-event analysis.

INTRODUCTION: Preventing smoking initiation will protect future generations from smoking-attributable death and disease. This study examines the correlates and patterns of initiation among Israeli youth using time-to-event analysis and other methods. METHODS: Twenty-four consecutive representative samples (1986-2009) of new military recruits (N=50,254) were analyzed. Cox regression and Kaplan-Meier analysis were used to identify factors associated with smoking initiation, and logistic regression was used to identify factors associated with smoking status. RESULTS: The most hazardous age for smoking initiation was seventeen, subsequent to the mean age of smoking initiation (males: 15.7, females: 16.0). Age of initiation and age of greatest hazard for initiation declined among recruits between the years 1986 and 2009. Earlier smoking initiation among boys and girls was significantly associated with low education levels (<12years) (males: HR=2.98, CI: [2.79, 3.18]; females: HR=3.35, CI: [2.96, 3.80]), low paternal education levels, Russian birthplace, and religion. Earlier initiation in boys was associated with high fitness levels and low/medium socio-economic status. Earlier initiation in girls was associated with being Western-born and ever-use of contraception. CONCLUSIONS: Smoking initiation among Israeli youth recruited to the armed forces is associated with individual and family characteristics, particularly low education levels. Time-to-event analysis complements traditional means of understanding smoking initiation by identifying ages at which initiation hazard is high.

Demographic and dietary predictors of urinary bisphenol A concentrations in adults in Israel.

BACKGROUND: To date, there is scarce data on levels of exposure to bisphenol A (BPA) in the general population in Israel and the region. The goal of the current study was to measure urinary levels of BPA in the general adult population in Israel and to determine the demographic and dietary predictors of exposure. METHODS: We recruited 249 individuals (ages 20-74) from five different regions in Israel. We collected urine samples and questionnaire data including detailed dietary data and analyzed urine samples for BPA concentrations. RESULTS: Eighty nine percent of the study population had urinary BPA concentrations equal to or above the level of quantification (0.3 µg/L). Median creatinine adjusted BPA urinary concentrations in the study population (2.3 µg/g) were slightly higher than those reported for the general population in the US (1.76 µg/g) and Canada (1.47 µg/g), and were comparable to those reported for the general population in Belgium (2.25 µg/g) and Korea (2.09 µg/g). BPA concentrations were higher in Jews compared to Arab and Druze (prevalence ratio (PR)=2.34; 95%CI 1.56-3.49), in individuals with higher education (PR=1.70, 1.11-2.62), in individuals consuming mushrooms (PR=2.08, 1.07-4.05), and in smokers (PR=1.43, 1.00-2.05). CONCLUSIONS: We found that the general adult population in Israel is widely exposed to BPA. Our findings on higher BPA levels in Jews compared to Arabs and Druze and in individuals with higher education highlights the fact that predictors of BPA exposure vary across populations.

Urinary concentrations of organophosphate pesticide metabolites in adults in Israel: demographic and dietary predictors.

Exposure to organophosphate pesticides (OPs) in agricultural and urban populations has been associated with a range of adverse health effects. The purpose of the current study was to estimate exposure to OPs in the general adult population in Israel and to determine dietary and demographic predictors of exposure. We measured six non-specific organophosphate pesticide metabolites (dialkyl phosphates) in urine samples collected from 247 Israeli adults from the general population. We collected detailed demographic and dietary data from these individuals, and explored associations between demographic and dietary characteristics and urinary dialkyl phosphate concentrations. OP metabolites were detectable in all urine samples. Concentrations of several dialkyl phosphate metabolites (dimethylphosphate, dimethylthiophosphate, diethylphosphate) were high in our study population relative to the general populations in the US and Canada and were comparable to those reported in 2010 in France. Total dialkyl phosphates were higher in individuals with fruit consumption above the 75th percentile. In a multivariate analysis, total molar dialkyl phosphate concentration increased with age and was higher in individuals with high income compared to individuals with the lowest income. Total diethyl metabolite concentrations were higher in females and in study participants whose fruit consumption was above the 75th percentile. In conclusion, we found that levels of exposure to OP pesticides were high in our study population compared to the general population in the US and Canada and that intake of fruits is an important source of exposure.

Urinary concentrations of environmental contaminants and phytoestrogens in adults in Israel.

BACKGROUND: The Ministry of Health Biomonitoring Study estimated exposure of individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP) pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and the phytoestrogenic compounds genistein and daidzein. METHODS: In 2011, 250 individuals (ages 20-74) were recruited from five different regions in Israel. Urine samples were collected and questionnaire data were obtained, including detailed dietary data (food frequency questionnaire and 24hour recall). Urinary samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate metabolites, cotinine, PAH metabolites, genistein, and daidzein. RESULTS AND DISCUSSION: BPA urinary concentrations were above the limit of quantification (LOQ) in 89% of the samples whereas urinary concentrations of phthalate metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ in 44-100% of the samples. All non-smoking participants had detectable levels of cotinine in their urine; 63% had levels above the LOQ, and the rate of quantification was high compared to the general non-smoking population in Canada. Median creatinine adjusted concentrations of several OP metabolites (dimethyl phosphate, dimethyl thiophosphate) were high in our study population compared to the general US and Canadian populations. Median creatinine adjusted urinary BPA concentrations in the study population were comparable to those in Belgium and Korea; higher than those reported for the general US, German, and Canadian populations; and very low compared to health-based threshold values. Phthalate concentrations were higher in our study population compared to the general US population but values were very low compared to health-based threshold values. Median creatinine adjusted PAH concentrations were generally comparable to those reported for the general US population; median creatinine adjusted daidzein concentrations were high in our population compared to the general US population whereas genistein concentrations were comparable. CONCLUSIONS: We interpreted observed urinary contaminant levels observed in our study by comparing values with health-based threshold values and/or values from international human biomonitoring studies. Using this data interpretation scheme, we identified two contaminants as being of potential public health concern and high priority for public health policy intervention: environmental tobacco smoke (ETS) and OP pesticides. We used the data collected in this study to support public health policy interventions. We plan to conduct a follow-up biomonitoring study in 2015 to measure ETS and OP exposure in the general population in Israel, to evaluate the effectiveness of relevant policy interventions.

Varicocoele among 1 300 000 Israeli adolescent males: time trends and association with body mass index.

Scarce data are available on epidemiology of varicocoele, the most common surgically correctable cause of male infertility. The objectives of this study were to evaluate the association between body mass index (BMI) and varicocoele and to assess trends in prevalence over time. We conducted a nationwide population-based long-term (1967-2010) study among 1 323 061 Israeli adolescent males using data from mandatory medical examination. BMI was grouped into underweight, normal weight, overweight and obese categories by percentiles adjusted for age in months and by further classification to five categories within normal weight. Univariable and multivariable logistic regression models were constructed, adjusting for possible confounders. Varicocoele prevalence (N = 47 398) increased during the study period from 1.6% for the 1950-1954 birth cohort to 4.6% for the 1990-1993 birth cohort, with the steepest rise in the normal weight group. Varicocoele unadjusted rates were highest (4.1%) among underweight and lowest (1.6%) among obese. In a multivariable model, adjusted for birth cohort, height, age and socio-demographic factors, we found a decreased risk for varicocoele in the overweight group [odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.49, 0.54] and the obese group (OR = 0.34, 95% CI: 0.32, 0.37), compared with the normal weight group. Within the normal weight group, a monotonic inverse association between BMI percentile and varicocoele was observed, most notable among 75-84.9 percentile compared to 25-49.9 percentile (OR = 0.65, 95% CI: 0.63, 0.68). In conclusion, varicocoele is common among adolescents in Israel, and its prevalence had increased in recent decades, providing clues to direct further andrological research on the role of modern lifestyle and environment in the aetiology of varicocoele. BMI, across percentiles, was found to be monotonically inversely associated with varicocoele, thus directing research and clinical efforts.